TORC1 and TORC2 work together to regulate ribosomal protein S6 phosphorylation in Saccharomyces cerevisiae

Article Article scientifique Article TORC1 and TORC2 work together to regulate ribosomal protein S6 phosphorylation in Saccharomyces cerevisiae eng 2016 author Yerlikaya Seda 681497 author Meusburger Madeleine 689452 author Kumari Romika author Huber Alexandre 525141 author Anrather Dorothea author Costanzo Michael author Boone Charles author Ammerer Gustav author Baranov Pavel V author Loewith Robbie Joséph 630703 397-409 10.1091/mbc.E15-08-0594 26582391 1059-1524 Nutrient-sensitive phosphorylation of the S6 protein of the 40S subunit of the eukaryote ribosome is highly conserved. However, despite four decades of research, the functional consequences of this modification remain unknown. Revisiting this enigma in Saccharomyces cerevisiae, we found that the regulation of Rps6 phosphorylation on Ser-232 and Ser-233 is mediated by both TOR complex 1 (TORC1) and TORC2. TORC1 regulates phosphorylation of both sites via the poorly characterized AGC-family kinase Ypk3 and the PP1 phosphatase Glc7, whereas TORC2 regulates phosphorylation of only the N-terminal phosphosite via Ypk1. Cells expressing a nonphosphorylatable variant of Rps6 display a reduced growth rate and a 40S biogenesis defect, but these phenotypes are not observed in cells in which Rps6 kinase activity is compromised. Furthermore, using polysome profiling and ribosome profiling, we failed to uncover a role of Rps6 phosphorylation in either global translation or translation of individual mRNAs. Taking the results together, this work depicts the signaling cascades orchestrating Rps6 phosphorylation in budding yeast, challenges the notion that Rps6 phosphorylation plays a role in translation, and demonstrates that observations made with Rps6 knock-ins must be interpreted cautiously. Mechanistic Target of Rapamycin Complex 1 Mechanistic Target of Rapamycin Complex 2 Multiprotein Complexes/metabolism Phosphorylation/physiology Polyribosomes/metabolism Protein-Serine-Threonine Kinases/metabolism Ribosomal Protein S6/genetics/metabolism Ribosome Subunits Small Eukaryotic/metabolism Ribosomes/metabolism Saccharomyces cerevisiae/metabolism Saccharomyces cerevisiae Proteins/metabolism Signal Transduction/genetics TOR Serine-Threonine Kinases/metabolism Transcription Factors/metabolism Dewey 570 Dewey 590 23 Institut de génétique et de génomique 0DH 43 Département de biologie moléculaire 161 false 814 Groupe Loewith Molecular Biology of the Cell 27 2 5989b811-fc28-4689-ac0b-c279cc94516b Article (Published version) Public MolBiolCell-2016-Yerlikaya-397-409.pdf 2354675 application/pdf openAccess Centres et instituts / Institut de génétique et de génomique Faculté des sciences / Section de biologie / Département de biologie moléculaire

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TORC1 and TORC2 work together to regulate ribosomal protein S6 phosphorylation in Saccharomyces cerevisiae	Molecular Biology of the Cell			2016	494	238

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Meusburger, Madeleine